Screening for Hyperbilirubinemia in Japanese Very Low Birthweight Infants Using Transcutaneous Bilirubinometry.

OBJECTIVES: To assess the accuracy of transcutaneous bilirubin (TcB) measurements at 5 different body sites in Japanese very low birthweight (VLBW) infants and to determine a cut-off value of TcB to detect total serum/plasma bilirubin (TB) levels ≥10 mg/dL (171 µM). STUDY DESIGN: In a prospective multicenter study, 85 Japanese VLBW infants were enrolled from 5 neonatal intensive care units during the study period. A total of 383 blood samples from infants not receiving phototherapy or ≥24 hours postphototherapy were analyzed. TcB was measured at the forehead, sternum, upper back, lower abdomen, and waist within 1 hour of blood collection. Linear regression analysis and Bland-Altman plots were used to compare TcB values at each site with TB levels. The TcB cut-off value for detecting TB ≥10 mg/dL was determined by receiver operating characteristics curve analysis. RESULTS: TcB significantly correlated with TB, but the coefficient of determination varied among the sites (forehead: 0.5294, sternum: 0.6488, upper back: 0.6321, lower abdomen: 0.5430, waist: 0.7396). At a TcB value ≥8, the sensitivity was 100% at the sternum and upper back, 85% at the waist, 84% at the forehead, and 64% at the lower abdomen to detect TB ≥10 mg/dL. CONCLUSIONS: In Japanese VLBW infants, the accuracy of TcB measurements varies according to body site. TcB ≥8 on the sternum or upper back is more reliable than that on the forehead, lower abdomen, or waist to detect TB levels ≥10 mg/dL.

Novel treatment strategy for Japanese newborns with high serum unbound bilirubin.

BACKGROUND: Serum unbound bilirubin (UB) is a measure of bilirubin not bound to albumin, and has been reported to be better than total bilirubin level at identifying infants at risk of developing bilirubin-induced neurotoxicity, including auditory abnormalities. A detailed treatment strategy for newborns with high serum UB has not been established. The aim of this study was to assess auditory outcomes in newborns with serum UB ≥1.00 µg/dL who were treated according to a novel treatment protocol. METHODS: A prospective clinical study was conducted in newborns weighing >1500 g with serum UB ≥1.00 µg/dL who were admitted to Kobe University Hospital and Kakogawa Municipal Hospital, Japan from 2006 to 2011. Enrolled newborns were treated as follows: (i) if serum UB was 1.00-1.50 µg/dL, phototherapy and infusion were given with or without albumin or immunoglobulin therapy; and (ii) if serum UB was >1.50 µg/dL, exchange transfusion was performed immediately. Auditory brainstem responses were evaluated at the time of discharge. RESULTS: A total of 89 Japanese newborns with UB ≥1.00 µg/dL were enrolled at a median age of 4 days. Of these, 85 had UB 1.00-1.50 µg/dL and four had UB >1.50 µg/dL. After being treated according to the protocol, no newborns were diagnosed with auditory brainstem response abnormalities. CONCLUSIONS: The present treatment protocol for Japanese newborns with serum UB ≥1.00 µg/dL may be useful for the prevention of bilirubin-induced auditory abnormalities.

Inhibition of heme oxygenase activity in newborn mice by azalanstat.

Inhibition of heme oxygenase (HO), the rate-limiting enzyme in heme catabolism, may be an ideal strategy for preventing neonatal jaundice. Although natural and synthetic heme analogs, called metalloporphyrins (Mps), have been extensively investigated for this purpose, some Mps are phototoxic, affect the activity of other enzymes, or induce HO-1 transcription-properties that may limit their clinical use. Another class of compounds, imidazole-dioxolanes, has been shown to selectively inhibit the inducible isozyme HO-1. Therefore, we investigated the efficacy of azalanstat (AZA), an imidazole-dioxolane, towards inhibiting HO activity in 7-day-old mice. We found that a single dose of AZA at 500 micromol.kg(-1) body mass (BM) administered i.p. significantly inhibited HO activity and reduced in vivo bilirubin production. In the spleen, HO inhibition (>50%) was observed within 0.25-3 h after administration. After 24 h, however, spleen HO activity, HO-1 protein, and HO-1 mRNA levels significantly increased 1.2-, 2.4-, and 4.0-fold, respectively. We conclude that AZA effectively inhibits in vivo HO activity only at a high dose and that it also induces spleen HO-1 gene transcription. Therefore, other imidazole-dioxolanes should be evaluated to determine whether they are more potent than AZA for use in treating neonatal jaundice.